Blood coagulation is a highly regulated process. Blood possess the potential to clot rapidly, but only at specific times and at specific sites. When clotting occurs, the majority of the blood is maintained in the fluid state. If this balance is upset, serious complications, including bleeding tendencies, heart attack, and stroke can arise. It is important, therefore, to understand in detail how the systems that control coagulation function. Protein Z is a-member of the vitamin K-dependent family of plasma proteins. The function of protein Z is not known, but based on its structural similarity to the other vitamin K-dependent proteins, we propose that protein Z plays a role in the regulation of blood coagulation. The goal of these studies is to elucidate the function of protein Z, and to relate the function of this protein to its structure. Towards this objective, the following studies will be carried out. 1. Thrombin may regulate the activity of protein Z. The location of the thrombin cleavage site in protein Z will be determined by isolating and sequencing the peptides obtained when protein Z is treated with thrombin. 2. Binding of phospholipid surfaces may be an important aspect of protein Z function. Protein Z binding to phospholipid vesicles will be studied by light scattering, and by fluorescence spectroscopy. 3. To test directly the hypothesis that protein Z plays a role in coagulation, the effects of protein Z on several procoagulant and anticoagulant reactions will be determined, both in plasma and in systems consisting of purified components. The effects of monoclonal antibodies directed against protein Z on these reactions will also be investigated.